Roles of the functional domains and conserved residues of the severe fever with thrombocytopenia syndrome virus L protein provide insights into the viral RNA transcription/replication mechanism

Zhiyun Yin; Fuli Ren; Min Zhou; Shengyao Chen; Yali Deng; Sijing Hu; Fei Deng; Shu Shen; Junming Shi

doi:10.1016/j.virs.2022.08.009

December 2022

. doi: 10.1016/j.virs.2022.08.009

Citation: Zhiyun Yin, Fuli Ren, Min Zhou, Shengyao Chen, Yali Deng, Sijing Hu, Fei Deng, Shu Shen, Junming Shi. Roles of the functional domains and conserved residues of the severe fever with thrombocytopenia syndrome virus L protein provide insights into the viral RNA transcription/replication mechanism .VIROLOGICA SINICA, 2022, 37(6) : 946-949. http://dx.doi.org/10.1016/j.virs.2022.08.009

发热伴血小板减少综合征病毒L蛋白功能域和保守残基研究为理解病毒RNA转录/复制机制提供新思路

尹志芸 ^a,b ,
任富利 ^a,c ,
周敏 ^a ,
陈声耀 ^a ,
邓雅丽 ^a ,
胡思靖 ^a ,
邓菲 ^a ,
沈姝 ^a,, ,
史君明 ^a,,

a 中国科学院武汉病毒研究所国家病毒资源中心;
b 沧州交通大学;
c 武汉金银潭医院转化医学中心

通讯作者： 沈姝, shenshu@wh.iov.cn; 史君明, sjm@wh.iov.cn
收稿日期： 2022-06-17
录用日期： 2022-08-26

摘要

发热伴血小板减少综合征病毒（SFTSV）是一种新的蜱传病毒病原体，致死率高，且缺乏有效药物和疫苗。SFTSV聚合酶蛋白L在基因组复制和转录中起着至关重要的作用。为了更好地理解L蛋白的功能机制，本研究通过基于报告基因的微复制子系统评估了L蛋白不同功能域及其保守氨基酸残基对SFTSV RNA合成的影响。结果表明各结构域对L蛋白的功能都至关重要，缺一不可。点突变结果显示12个保守氨基酸位点中，有9个位点氨基酸突变严重影响微复制子报告基因的表达，表明这9个位点是SFTSV L中的关键位点，对于L蛋白功能有重要作用。上述研究结果将有助于对SFTSV-L蛋白结构及其对病毒RNA转录和复制机制的理解。近年来，与SFTSV密切相关的新病毒不断被发现，且有证据表明这类SFTSV相关的新病毒具有感染人/动物并致病的风险，对公共卫生构成潜在威胁。序列比对结果表明SFTSV L蛋白中的关键氨基酸位点在这类SFTSV相关新病毒中高度保守，提示L蛋白可作为研制抗病毒药物的重要靶点，为广谱抗SFTSV相关病毒的药物研发提供思路。
- SFTSV
- , RdRp蛋白
- , 微复制子
- , 保守位点
- , 抗SFTSV药物

Roles of the functional domains and conserved residues of the severe fever with thrombocytopenia syndrome virus L protein provide insights into the viral RNA transcription/replication mechanism

Zhiyun Yin ^a,b ,
Fuli Ren ^a,c ,
Min Zhou ^a ,
Shengyao Chen ^a ,
Yali Deng ^a ,
Sijing Hu ^a ,
Fei Deng ^a ,
Shu Shen ^a,, ,
Junming Shi ^a,,

a National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China;
b Academic Affairs Office of Cangzhou Jiaotong University, Cangzhou, 061199, China;
c Center for Translational Medicine, Jinyintan Hospital, Wuhan, 430023, China

Corresponding author: Shu Shen, shenshu@wh.iov.cn Junming Shi, sjm@wh.iov.cn
Received Date: 17 June 2022
Accepted Date: 26 August 2022

Abstract

Highlights
1. All the domains of SFTSV-L protein were required for its function in viral RNA replication/transcription.
2. The influence of twelve conserved residues speculated basing on the atomic model of SFTSV-L were evaluated using mini-genome system, and nine of which showed significant roles in the function of L protein.
3. Nine key residues of SFTSV-L were strictly conserved among emerging related phleboviruses, suggesting L protein may be a promising broad spectrum drug target of phleboviruses.

References
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通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142

Roles of the functional domains and conserved residues of the severe fever with thrombocytopenia syndrome virus L protein provide insights into the viral RNA transcription/replication mechanism

Corresponding author: Shu Shen, shenshu@wh.iov.cn

Corresponding author: Junming Shi, sjm@wh.iov.cn

a National Virus Resource Center, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, 430071, China;

b Academic Affairs Office of Cangzhou Jiaotong University, Cangzhou, 061199, China;

c Center for Translational Medicine, Jinyintan Hospital, Wuhan, 430023, China

Received Date: 17 June 2022

Accepted Date: 26 August 2022

Abstract: Highlights
1. All the domains of SFTSV-L protein were required for its function in viral RNA replication/transcription.
2. The influence of twelve conserved residues speculated basing on the atomic model of SFTSV-L were evaluated using mini-genome system, and nine of which showed significant roles in the function of L protein.
3. Nine key residues of SFTSV-L were strictly conserved among emerging related phleboviruses, suggesting L protein may be a promising broad spectrum drug target of phleboviruses.

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发热伴血小板减少综合征病毒L蛋白功能域和保守残基研究为理解病毒RNA转录/复制机制提供新思路

摘要

Roles of the functional domains and conserved residues of the severe fever with thrombocytopenia syndrome virus L protein provide insights into the viral RNA transcription/replication mechanism

Abstract

References

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Electronic Supplementary Material

Article Metrics

Related

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通讯作者: 陈斌, bchen63@163.com